Journal
NATURE COMMUNICATIONS
Volume 8, Issue -, Pages -Publisher
NATURE PUBLISHING GROUP
DOI: 10.1038/s41467-017-00622-4
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Funding
- Translational Resource Center of the National Research Program for Biopharmaceuticals [NSC102-2325-B-001-023]
- Academia Sinica Genomic Medicine Multicenter Study [40-05-GMM]
- National Science Council Research grant [NSC 102-2314-B-182-053-MY3]
- Academia Sinica Research Program on Nanoscience and Nanotechnology and Translational Resource Center for Genomic Medicine (TRC) of the National Research Program for Biopharmaceuticals (NRPB), Taiwan [MOST103-2325-B-001-017]
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Conjugation of polyethylene glycol (PEG) to therapeutic molecules can improve bioavailability and therapeutic efficacy. However, some healthy individuals have pre-existing antiPEG antibodies and certain patients develop anti-PEG antibody during treatment with PEGylated medicines, suggesting that genetics might play a role in PEG immunogenicity. Here we perform genome-wide association studies for anti-PEG IgM and IgG responses in Han Chinese with 177 and 140 individuals, defined as positive for anti-PEG IgM and IgG responses, respectively, and with 492 subjects without either anti-PEG IgM or IgG as controls. We validate the association results in the replication cohort, consisting of 211 and 192 subjects with anti-PEG IgM and anti-PEG IgG, respectively, and 596 controls. We identify the immunoglobulin heavy chain (IGH) locus to be associated with anti-PEG IgM response at genome-wide significance (P = 2.23 x 10(-22)). Our findings may provide novel genetic markers for predicting the immunogenicity of PEG and efficacy of PEGylated therapeutics.
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